Sex-Specific Transcriptomic Profiles in Psoriatic Lesions: A Large-Scale Integrative Study

Area of Science:

• Dermatology
• Immunology
• Genomics

Background:

• Psoriasis is a chronic inflammatory skin condition with known gender-based variations in severity and treatment outcomes.
• Despite extensive research into psoriasis mechanisms, sex-specific molecular differences remain largely uncharacterized.

Purpose of the Study:

• To investigate sex-specific transcriptomic differences in lesional psoriasis skin.
• To identify molecular pathways and upstream regulators that differ between male and female psoriasis patients.

Main Methods:

• Comprehensive analysis of transcriptomic data from lesional psoriasis skin and healthy controls in male and female cohorts.
• Identification of overlapping and sex-specific differentially expressed genes (DEGs).
• Upstream regulator analysis to identify sex-specific drivers.

Main Results:

• 2760 overlapping DEGs were identified, with shared pathways including IL-17 signaling and Th17 differentiation.
• Male-enriched pathways included PI3K-Akt signaling and chemokine receptor activity.
• Female-enriched pathways included glycolysis and AHR-NRF2 signaling. Sex-specific upstream regulators and differences in Regulatory T cells (Tregs) and neutrophil abundance were also noted.

Conclusions:

• Significant sex-associated molecular and cellular disparities exist in psoriasis.
• These findings highlight potential sex-specific mechanisms influencing disease manifestation and treatment response.
• This exploratory study provides a foundation for future research into sex-specific psoriasis therapies.